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PubMed2001

A case of persistent acute allograft glomerulopathy with long-standing stable renal function.

Acute allograft glomerulopathy (AAG) characterized by hypercellularity, enlargement of endothelial cells, infiltration of glomeruli by mononuclear cells and webs of PAS-positive material has been reported as an unusual but distinct form of acute rejection in kidney transplant recipients. We present a case of persistent AAG proven by serial biopsies. The patient was 53 years old when she received kidney transplantation from her mother. The immunosuppressants were methylprednisolone, azathioprine and FK506. She developed several acute rejections and received antirejection therapy. The patient transferred to our hospital 15 months after transplantation. Serum creatinine was 2.11 mg/dL. The level of serum creatinine was gradually elevated from 2.11 mg/dL to 3.09 mg/dL. Graft biopsy, performed 16.5 months after transplantation, represented prominent intraglomerular infiltration of mononuclear cells, segmental thickening of glomerular basement membrane (GBM) with double contour, grade 1 tubulitis, marked accumulation of mononuclear cells in peritubular capillaries and margination of mononuclear cells in a small artery. It was diagnosed as acute allograft glomerulopathy (AAG). Intravenous methylprednisolone pulse therapy, discontinuation of FK506 and administration of cyclosporin (CYA) resulted in decrease of serum creatinine. To evaluate histological evolution of AAG we performed two subsequent biopsies over 3 yr. Severe glomerulitis persisted as a prominent feature 8 months later and still existed 53.4 months after transplantation with decreased severity. The extent of GBM reduplication also decreased, but the percentage of glomerular sclerosis increased gradually. Multi-layering of basement membrane of peritubular capillary and interstitial fibrosis also increased. The prominence of infiltration of mononuclear cells in peritubular capillary was unchanged. At the last follow-up, i.e. 71 months after transplantation, her serum creatinine was 1.34 mg/dL. Neither proteinuria nor haematuria was observed. We consider that our immunosuppressive treatment has been successful so far, because the patient is still maintaining stable graft function since the transplantation over 6 yr ago. It is thus suggested that AAG per se probably has no influence on acute aggravation of graft function, but AAG and capillaritis in peritubular capillaries may cause an evolution of chronic allograft nephropathy, resulting in a slowly progressive deterioration of graft function.

Acute Disease↗

PubMed2000

De novo induction of endothelial L-selectin ligands during kidney allograft rejection.

Acute kidney allograft rejection is characterized by a lymphocyte infiltration. L-selectin on lymphocytes and its endothelial glycosylated ligands are instrumental in the initiation of lymphocyte extravasation to sites of inflammation. From more than 500 core biopsy specimens taken from kidneys after transplantation, 250 biopsies were graded to have signs of acute rejection. Of these, 52 biopsies with various grades of histologic signs of acute rejection were selected for the study. Controls were 15 biopsies taken within 30 min after revascularization and 10 specimens from well-functioning allografts showing no clinical or histologic evidence of rejection. Immunochemical stainings with monoclonal antibodies against functionally active decorated L-selectin ligands. i.e., sialyl-Lewis x (sLex, 2F3 and HECA-452) or sulfated lactosamine (MECA-79) were performed. Although no endothelial 2F3 and MECA-79 epitopes were detected in nonrejecting control specimens, the expression was induced at the onset and during acute allograft rejections. The level of expression (in semi-quantitative score) of 2F3 reactivity correlated with the severity of rejection (P<0.0001, grade I versus grade IIB), and the level of expression decreased as the rejection resolved. Kidney biopsies taken shortly after revascularization and thus undergoing reperfusion injury showed endothelial staining with another anti sLex antibody, HECA-452. This staining disappeared from well-functioning grafts and reappeared at the onset of an acute allograft rejection. These results suggest that expression of functionally active, properly glycosylated L-selectin ligands might have a role in reperfusion injury and in the initiation of acute rejections after human kidney allograft transplantation.

Amino Sugars↗

PubMed1985

Impact of cyclosporine on renal transplant practice at the University of Texas Medical School at Houston.

CsA has improved the outcome of renal allotransplantation with CAD and LRD kidneys. CsA mitigates risk factors heretofore presenting substantial obstacles to CAD transplantation: HLA matching, pretransplant splenectomy, extensive numbers of conditioning blood transfusions, and old age. In LRD transplantation, CsA obviates the need for donor-specific transfusions in the haploidentical situation, and for prednisone in the HLA-identical setting. The incidence of drug-induced nephrotoxicity beyond six months is 30% with the degree of dysfunction proportionate to the degree of histo-incompatibility, suggesting that subclinical allograft rejection due to overzealous dose reduction may compromise allograft function. At present, total conversion from CsA to Aza appears ill-advised; even patients who never suffered allograft rejection under CsA therapy frequently lose their allograft when the inferior level of Aza suppression is substituted. Drug-induced hypertension, a modestly significant factor, diminishes further by two years posttransplant. The benefit of CsA therapy is a reduced incidence of 19% initial and 10% recurrent rejection episodes. Of great importance is the observation that 17% of rejection episodes followed patient noncompliance. Further, the incidence of bacterial infections was greatly reduced, and viral infections modestly lessened. Only the occurrence of pneumocystis carinii was increased, but 92% of patients survived in spite of serious pulmonary infection. Development of a consistent CsA regimen has reduced the median initial hospitalization to 12.5 days for LRD and 14 days for CAD, a level well within the range stipulated for the Disease-Related Guidelines of the Medicare Program. Furthermore, readmission is less frequent; one-third of patients never reenter the hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2001

Tacrolimus rescue therapy for children with acute renal transplant rejection.

Seventeen children with renal transplants (11 living-related, age 2-18 years) were converted from cyclosporine to tacrolimus because of acute rejection that failed to respond to high-dose corticosteroids. Resistance to corticosteroids was confirmed by renal biopsy in 14 patients, and assumed in 3 patients because of failure of serum creatinine to improve to baseline values. Four patients were also treated with OKT3, and 15 children had been receiving mycophenolate maintenance therapy prior to conversion to tacrolimus. Rejection occurred at 2-174 weeks post transplant (mean 52 weeks). Actuarial 1- and 2-year graft survival was 87% and 78%. Three children progressed to end-stage renal disease after 4, 12, and 13 months of tacrolimus. The remaining 14 children have functioning allografts after 20-168 weeks of treatment (mean 80 weeks). All 14 children exhibit stable or improved renal function: serum creatinine 1.1+/-0.7 mg/dl versus 2.0+/-0.9 mg/dl prior to tacrolimus. In conclusion, tacrolimus was effective therapy for both early and late acute rejection in children who failed to respond to high-dose corticosteroids. No significant short-term adverse effects were encountered.

Acute Disease↗

PubMed1986

The outcome of 304 primary renal transplants in children (1968-1985).

Of 304 children who received primary renal transplants at the University of Minnesota between January 1, 1968, and December 31, 1985, 48 (16%) were under the age of 24 months, 60 (20%) were 2-5 years old, and 196 (64%) were 6-17 years old at transplantation. Currently, 254 (84%) are alive at 2 months to 18 years following their first transplants, 77% with functioning grafts (188 first, 45 retransplants) and 7% on dialysis. Overall, patient and graft survival were not significantly different from the primary graft outcome of nondiabetic adults. The actuarial primary graft function rates at 1, 5, and 10 years were 100, 100, and 90% in 16 HLA-identical sibling kidneys; 84, 64, and 52% in 210 mismatched related kidneys; and 72, 54, and 47% in 78 cadaver kidneys (p less than 0.002). The 1-year patient survival and primary graft function rates in 44 mismatched related recipients under the age of 24 months were 92 and 88%. The use of deliberate, pretransplant random blood transfusion since 1979 has been associated with a decreased rejection rate. Primary graft function of mismatched related kidneys in children receiving standard immunosuppression has significantly improved from 78% at 1 year in the pretransfusion era to 91% (p less than 0.01) in the transfusion era. The overall primary cadaver graft function rate, however, did not improve in the transfusion era. Whether cyclosporine use will improve the cadaver renal allograft function in very young recipients remains to be established. However, with the use of related donors, even very young children can be transplanted safely and with excellent results.

Adolescent↗

PubMed2004

A systematic review of laparoscopic live-donor nephrectomy.

BACKGROUND: A systematic review was undertaken to assess the safety and efficacy of laparoscopic live-donor nephrectomy (LLDN) compared with open live-donor nephrectomy (OLDN). METHODS: Literature databases were searched from inception to March 2003 inclusive. Comparative studies of LLDN versus OLDN (randomized and nonrandomized) were included. RESULTS: There were 44 included studies, and the quality of the available evidence was average. There was only one randomized controlled trial and six nonrandomized comparative studies with concurrent controls identified. In terms of safety, for donors, there did not seem to be any distinct difference between the laparoscopic and open approaches. No donor mortality was reported for either procedure, and the complication rates were similar although the types of complications experienced differed between the two procedures. The conversion rate for LLDN to an open procedure ranged from 0% to 13%. In terms of efficacy, LLDN seemed to be a slower operation with longer warm ischemia times than OLDN, but this did not seem to have resulted in increased rates of delayed graft function for recipients. Donor postoperative recovery and convalescence seemed to be superior for LLDN, making it a potentially more attractive operation for living donors. Although in the short-term, graft function and survival did not seem to differ between the two techniques, long-term complication rates and allograft function could not be determined and further long-term follow-up is required. CONCLUSIONS: LLDN seems to be at least as safe and efficacious as OLDN in the short-term. However, it remains a technique in evolution. Further high-quality studies are required to resolve some of the outstanding issues surrounding its use, in particular, long-term follow-up of donor complications and recipient graft function and survival.

Humans↗

PubMed1997

The role of donor and recipient B7-1 (CD80) in allograft rejection.

Blockade of CD28-mediated T cell costimulatory signals produces effective immunosuppression of a variety of T cell-dependent in vivo immune responses, including autoimmune disorders and transplant rejection. The soluble fusion protein CTLA4Ig, which competitively blocks CD28 ligands B7-1 and B7-2, can prevent allograft and xenograft rejection and in some circumstances induce transplantation tolerance. To determine the relative roles of B7-1 and B7-2 in graft rejection, we have performed islet and cardiac allografts with normal and B7-1(-/-) mice in conjunction with selective blocking reagents. We found that the absence of B7-1 on donor or recipient tissues leads to a slight prolongation of islet allograft survival, but has minimal or no effect on cardiac allograft survival. Allograft function is further prolonged in the islet model when both donor and recipient lack B7-1, although cardiac allograft survival is not prolonged. In the cardiac model, treatment with CTLA4Ig induces long term survival in B7-1(-/-) recipients regardless of donor status. In contrast, anti-B7-2 mAb leads to indefinite allograft survival only when the recipient and donor both lack B7-1, indicating that even in the absence of available B7-2, B7-1 molecules on the donor or recipient cells alone are sufficient to induce graft rejection. These data also indicate that B7-1 and B7-2 are the only CD28 ligands relevant to cardiac allograft rejection in mice.

Animals↗

PubMed1995

Spontaneous improvement of renal function following renal allograft rupture associated with acute rejection.

A renal allograft recipient developed acute cellular rejection 7 days after her second cadaveric renal transplantation. Her renal function failed to improve after three 0.5 g pulses of intravenous Methylprednisolone therapy. Spontaneous renal allograft rupture occurred 4 days later, which was successfully salvaged surgically. There was spontaneous rapid improvement of renal function with marked diuresis immediately following the allograft rupture, without additional immunosuppressive therapy. Her clinical course illustrates that delayed improvement of renal allograft function can be a consequence of raised intra-renal pressure during acute rejection. In addition, intensification of anti-rejection therapy is not an absolute requirement in all cases of rejection-associated renal allograft rupture.

Acute Disease↗

PubMed1996

Prostaglandin E1 administration following orthotopic liver transplantation: a randomized prospective multicenter trial.

BACKGROUND & AIMS: Prostaglandin E1 (PGE1) has been used after orthotopic liver transplantation (OLT) based on limited clinical data suggesting PGE1 infusion improves immediate hepatic allograft function. The aim of this study was to conduct a randomized double-blinded multicenter trial to evaluate the effect of PGE1 on early hepatic and renal function in patients undergoing OLT. METHODS: One hundred eighteen patients were randomized to receive either PGE1 or crystalloid placebo intravenously after allograft revascularization. Primary end points were incidence of primary allograft nonfunction (PNF) or severe renal dysfunction. RESULTS: The incidence of PNF was 6.7% (4 of 60) and 6.9% (4 of 58) in the control and PGE1 groups, respectively. PGE1 infusion was, however, associated with improved early renal function (mean peak creatinine level of 1.4 +/- 1.0 and 2.0 +/- 1.0 in patients treated with PGE1 and placebo, respectively; P < 0.001). Severe renal dysfunction occurred more frequently in the placebo group (26.7%) than in the PGE1 group (13.8%; P = 0.65). Additionally, dialysis treatments were more frequent in the placebo group (0.7 +/- 2.0 per patient) than in the PGE1 group (0.2 +/- 1.0 per patient; P = 0.10). Initial intensive care unit stay was shorter in patients treated with PGE1 (4.0 +/- 3.6 days) compared with controls (10.5 +/- 17.1 days) (P < 0.01). CONCLUSIONS: PGE1 administration after OLT resulted in improved renal function and decreased initial postoperative intensive care unit stay but did not affect the incidence of PNF.

Adult↗

PubMed2004

Strategies to prevent chronic allograft nephropathy in kidney transplantation: focus on calcineurin inhibitors.

Chronic allograft nephropathy is one of the leading causes of long-term graft failure in kidney transplant recipients. The etiology of this condition is multifactorial, but administration of calcineurin inhibitors is often implicated. With the introduction of newer immunosuppressive agents, strategies for calcineurin inhibitor minimization, avoidance, and withdrawal have been emerging in the literature. These strategies may improve long-term kidney allograft function, but are not without risks. Results from recent clinical trials evaluating the safety and efficacy of these strategies to prevent chronic allograft nephropathy in kidney transplant recipients are summarized and reviewed. Patients who had never received a calcineurin inhibitor or who had cyclosporine withdrawn from their regimens had better kidney function than patients who received or kept receiving a calcineurin inhibitor. The impact of the improvement in kidney function on long-term graft survival remains to be determined. In addition, the benefit in renal function must be weighed against the bone marrow toxicities and/or metabolic complications associated with these regimens.

Alemtuzumab↗

PubMed1975

Low dose heparin and early kidney transplant function.

A prospective randomised double blind trial was carried out to assess the effect of subanticoagulant doses of subcutaneous heparin (Calciparine) compared to placebo on early renal allograft function. Thirty-six patients were entered into the trial, 18 received placebo and 18 heparin. There was no significant difference between the patients in either group in respect to early graft function, the number of rejection episodes or the response of graft function to treatment of rejection. There were four patients with haemorrhagic complications who had received heparin, whereas no patients in the placebo group had bleeding combinations. It is concluded that subanticoagulant doses of heparin have no demonstrable effect on early graft function and may cause haemorrhagic complications.

Adolescent↗

PubMed2006

Application of machine perfusion preservation as a viability test for marginal kidney graft.

BACKGROUND: This study evaluated the usefulness of machine perfusion preservation parameters as indicators of kidney graft viability. METHODS: Eighty-eight cadaveric kidneys were analyzed in this study. Of these, 74 kidneys (84.1%) were procured from nonheartbeating donors. The criteria for an acceptable kidney for transplantation were a perfusion flow of more than 0.4 mL/min/g with a concurrent decreasing perfusion pressure. The average perfusion pressure was 30-50 mmHg. We divided the kidneys into three groups: group 1 (n=35), 0.45-0.65 mL/min/g machine perfusion flow (MPF); group 2 (n=30), 0.65-0.90 mL/min/g MPF; and group 3 (n=23), more than 0.9 mL/min/g MPF. RESULTS: A higher rate of primary nonfunction (PNF; 25.7%) was found in group 1, compared with 6.7% in group 2 and 0% in group 3. A higher rate of 30.4% immediate function was found in group 3, compared with 16.7% in group and 8.6% in group 1. However, a longer period of acute tubular necrosis (ATN; 12.0 days) was found in group 1 compared with 8.6 days in group 2 and 8.7 days in group 3. PNF was detected in 7 (77.8%) cases with more than 16 hr of total ischemic time (TIT) in group 1. In contrast, all of nine cases with more than 16 hr of TIT in group 3 were functional. CONCLUSIONS: MPF is a reliable indicator of graft viability based on the rate of PNF and immediate renal allograft function, especially in marginal donors.

Adult↗

PubMed1994

Aortic valve replacement in the young.

The attractiveness of the aortic allograft in any form, whether it be free style or root, is the high 10-year freedom from thromboembolism, absence of requirement for anticoagulants, use in active infections, excellent hemodynamics, and freedom from reoperation. The 10-year freedom from all valve related complications has been reported to be around 92% versus only 75% for the porcine bioprosthetic valve. Gradients across the allograft aortic valve are comparable to that of the St. Jude valve (St. Jude Medical, St. Paul, MN, USA) with valve areas approaching 2 cm2 in the extremely large homograft. Between November 1986 and September 1993, the author used the aortic allograft as a freehand procedure in 51 patients and for root replacement in 22 patients. Stimulus for use of limited root replacement with the allograft in aortic valve replacement has occurred because of the unpredictability of the freehand operation with regard to valve insufficiency. This has been done in spite of the Ross modification of retaining the noncoronary sinus. Evaluation of freehand allograft function by echo analysis has demonstrated an unacceptable incidence of insufficiency not found when a small segment of the allograft root is used. The native coronary arteries, however, must be transposed to the donor root, which of itself has the potential of introducing new problems not seen with other valve substitutes. Complications with the freehand allograft have consisted of explanation in eight patients, four early and four late. Six of the early and late explanations have been for insufficiency. Techniques of valve and valve root implantation will be presented in detail.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Valve↗

PubMed1982

Renal allograft rupture: a report of three cases and review of the literature.

This report reviews the features of 149 cases of renal allograft rupture, while adding a detailed description of 3 more cases to the English literature. From November, 1973 to November, 1979, 3 cases of renal allograft rupture occurred in 100 renal transplants performed at Research Medical Center, Kansas City, Mo., an incidence of 3.0%. Rupture developed between the 6th and 8th day after transplantation while patients required dialysis because of poor allograft function. All patients had surgical exploration and successful repair of laceration. Clinical and/or histological findings were consistent with acute rejection in all 3 cases. One graft functioned for 5 years with gradual loss of function. The other two grafts are functioning at the present time. Review of reported cases suggests that acute rejection is the most common cause of allograft rupture. Rupture of the renal allograft did not appear to increase the intensity of rejection, nor did it represent an irreversible rejection. Transplant nephrectomy can be avoided unless hemorrhage is uncontrollable from the site of laceration.

Adolescent↗

PubMed1996

An examination of tissue chimerism in the ACI to Lewis rat cardiac transplant model.

While the existence of chimeric cells in host tissue following organ transplantation is well documented, its distribution, temporal evolution and relationship to allograft survival is less clear. To explore this phenomenon, Lewis recipients of ACI cardiac allografts representing a wide range of immunosuppressive protocols and graft survival times were examined for the presence of chimerism using a sensitive polymerase chain reaction assay. Four groups of animals were examined: untransplanted animals receiving donor specific transfusion (DST)/cyclosporine A (CsA); allograft recipients with no treatment; recipients treated with DST/CsA/supplementary immunosuppression with rejection at 21-183 days; and recipients sacrificed with functioning allografts, treated with DST/CsA/supplementary immunosuppression and surviving > 200 days. To elucidate variations in the tissue distribution of chimeric cells, bone marrow, skin, liver, spleen, and thymus were examined in each animal. Untransplanted animals receiving DST/CsA displayed no evidence of chimerism. In animals receiving a cardiac allograft but no treatment, there was extensive evidence of chimerism in four of five animals. Chimerism was also detected in seven of nine animals with intermediate graft survival at the time of rejection. In animals with long-term graft survival, only four of eight displayed chimerism. These results suggest that, without immunosuppression, early chimerism does not lead to prolonged graft survival and that, even when graft survival is moderately prolonged, these cells are not sufficient to prevent rejection. In conclusion, chimerism appears to be a common phenomenon following transplantation, is not a result of DST, and may not be necessary for maintenance of long-term graft survival.

Animals↗

PubMed2002

Recombinant human growth hormone post-renal transplantation in children: a randomized controlled study of the NAPRTCS.

BACKGROUND: Growth retardation persists in renal allograft recipients despite successful transplantation. The etiology is multi-factorial including the adverse effects of corticosteroids, suboptimal allograft function, and perturbations of the GH/GF axis. Recombinant human growth hormone (rhGH) has been effective in improving growth velocity; however, allograft dysfunction has been reported. Therefore, a randomized controlled study was undertaken. METHODS: Sixty-eight growth retarded pediatric renal allograft recipients were enrolled in a one-year randomized controlled study to determine the efficacy and safety of rhGH. A protocol biopsy was performed prior to enrollment. RESULTS: After one year, the delta SDS (standardized height) was +0.49 +/- 0.10 in the treatment group (N = 30) compared to -0.10 +/- 0.08 in the control group (N = 22; P < 0.001). During the first year, there were no rejection episodes in the treatment group and three in the control group. After the first year, when all recipients were receiving rhGH, there were three patients in the treatment group and two patients in the control group who experienced an acute rejection episode. Prior to enrollment, more than one acute rejection episode was predictive of a subsequent rejection following enrollment. There was no difference in adverse events between the two groups. CONCLUSION: In conclusion, rhGH is effective in improving the growth velocity of pediatric renal allograft recipients and is not associated with an increase in adverse events.

Adolescent↗

PubMedDate not supplied

Evaluation of the clinical and histologic features of renal allograft rejection in cats.

OBJECTIVES: To describe the clinical signs and histopathologic features of renal allograft rejection in cats, and to provide a historical, untreated control group for use in future studies of feline renal allograft rejection. ANIMALS: Fourteen adult research cats. METHODS: Renal transplantation and bilateral nephrectomy were performed in pairs of immunogenically mismatched cats. A physical examination was performed, and packed cell volume, total protein, and plasma creatinine concentrations were measured each day after surgery. The cats were euthanatized when plasma creatinine concentration exceeded 7 mg/dL or when weight loss exceeded 20%. Renal histopathology was scored according to the Banff 97 criteria by 3 pathologists. RESULTS: Nine cats completed the study. Plasma creatinine exceeded 7 mg/dL in 5 cats, weight loss exceeded 20% in 3 cats, and 1 cat was found dead. Clinical signs in cats with rejection were nonspecific or absent. Rectal temperature decreased by 0.8 +/- 0.5 degrees C in the 24 hours before euthanasia. The pathologists agreed on the allograft histopathologic category in 6 of 9 cats. The histologic consensus was acute/active rejection in 8 cats and normal in 1 cat. Median survival time of the 8 cats with histologically confirmed allograft rejection was 23 days (range, 8-34 days). CONCLUSIONS AND CLINICAL RELEVANCE: Renal allograft rejection is associated with minimal clinical signs. Therefore, plasma creatinine concentration should be measured routinely in patients with a functioning allograft. An increase in plasma creatinine concentration is highly suspicious for allograft rejection, although a biopsy of the renal allograft is needed for definitive diagnosis.

Animals↗

PubMed2006

Preemptive retransplantation for BK virus nephropathy: successful outcome despite active viremia.

BK virus nephropathy (BKVN) is now recognized as a major cause of renal allograft loss. Recent reports suggest that retransplantation in patients with graft loss due to BKVN is safe after return to dialysis. Since early transplantation is associated with improved outcomes, it would be advantageous if this procedure could be performed prior to ultimate graft loss. However, little data are available regarding the safety of this approach during active viremia. In this report, we describe successful preemptive retransplantation with simultaneous allograft nephrectomy in two patients with active BKVN and viremia at the time of surgery. With 21- and 12-month follow-up, respectively, both patients have stable allograft function and no evidence for active viral replication. We conclude that preemptive retransplantation can be considered in patients with failing allografts due to BKVN.

Adult↗